Understanding shared pathogenesis between chronic obstructive pulmonary disease (COPD) and lung cancer by means of cell specific genomics

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Green, Clara Emily (2018). Understanding shared pathogenesis between chronic obstructive pulmonary disease (COPD) and lung cancer by means of cell specific genomics. University of Birmingham. Ph.D.

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Abstract

Introduction: COPD (Chronic Obstructive Pulmonary Disease) and lung cancer are related conditions associated with inflammation. Relatively little focus has been given to the endothelium, through which inflammatory cells transmigrate to reach the lung. We sought to determine if coding and non-coding alterations in pulmonary endothelium exist in COPD and lung cancer.

Methods: Patients with and without COPD undergoing thoracic surgery were recruited. Pulmonary Endothelial Cells were isolated from lung and tumour and extracted RNA (ribonucleic acid) used for miRNA (micro-RNA) and mRNA (messenger RNA) microarrays. Ingenuity pathway analysis (IPA) was also carried out.

Results: 2071 genes and 43 miRNAs were significantly upregulated in COPD. 4 targets were validated by quantitative polymerase chain reaction, of which miR-181b-3p was chosen for functional validation. Another target, miR-429, was also increased in lung tumour. Several cancer-related pathways such as transforming growth factor- β were altered in the IPA. There was significantly reduced tube formation and endothelial sprouting in Human umbilical vein endothelial cells transfected with miR-181b-3p, consistent with an effect on angiogenesis.

Conclusions: Upregulation of miR-181b-3p reduces tube formation and sprouting by endothelial cells. This might be significant in the development of emphysema as lung vasculature is important in the structural maintenance of alveoli.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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